title: A noncanonical, GSK3-independent pathway controls postprandial hepatic glycogen deposition.
abstract: Insulin rapidly suppresses hepatic glucose production and slowly decreases expression of genes encoding gluconeogenic proteins. In this study, we show that an immediate effect of insulin is to redirect newly synthesized glucose-6-phosphate to glycogen without changing the rate of gluconeogenesis. This process requires hepatic Akt2, as revealed by blunted insulin-mediated suppression of glycogenolysis in the perfused mouse liver, elevated hepatic glucose production during a euglycemic-hyperinsulinemic clamp, or diminished glycogen accumulation during clamp or refeeding in mice without hepatic Akt2. Surprisingly, the absence of Akt2 disrupted glycogen metabolism independent of GSK3α and GSK3β phosphorylation, which is thought to be an essential step in the pathway by which insulin regulates glycogen synthesis through Akt. These data show that (1) the immediate action of insulin to suppress hepatic glucose production functions via an Akt2-dependent redirection of glucose-6-phosphate to glycogen, and (2) insulin increases glucose phosphorylation and conversion to glycogen independent of GSK3.
authors.affiliation: The Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Wan
authors.forename: Karla F
authors.initials: KF
authors.lastname: Leavens
authors.forename: Roger W
authors.initials: RW
authors.lastname: Hunter
authors.forename: Shlomit
authors.initials: S
authors.lastname: Koren
authors.forename: Alexander
authors.initials: A
authors.lastname: von Wilamowitz-Moellendorff
authors.forename: Mingjian
authors.initials: M
authors.lastname: Lu
authors.forename: Santhosh
authors.initials: S
authors.lastname: Satapati
authors.forename: Qingwei
authors.initials: Q
authors.lastname: Chu
authors.forename: Kei
authors.initials: K
authors.lastname: Sakamoto
authors.forename: Shawn C
authors.initials: SC
authors.lastname: Burgess
authors.forename: Morris J
authors.initials: MJ
authors.lastname: Birnbaum
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D015309:Glucose Clamp Technique; D019298:Glucose-6-Phosphate / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism*; D038362:Glycogen Synthase Kinase 3 / Q000502:physiology*; D050261:Glycogenolysis / Q000502:physiology*; D006946:Hyperinsulinism / Q000378:metabolism / Q000503:physiopathology; D007328:Insulin / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019518:Postprandial Period / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D007328:Insulin; D019298:Glucose-6-Phosphate; D006003:Glycogen; C494922:Akt2 protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3